Clinical significance of the CALLY index in patients with gastric cancer undergoing gastrectomy.

BACKGROUND: The aim of this study was to elucidate the clinical impact of the CALLY index in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2014 and December 2020, 617 patients who underwent gastrectomy for GC at the Osaka City General Hospital were enrolled in this study. The CALLY index was calculated using the following formula: [albumin (g/dL) × lymphocytes (/µl)]/[CRP (mg/dL) × 104]. We compared the predictive value of four biomarkers [CALLY index, modified Glasgow prognostic score (mGPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR)] for short- and long-term outcomes and focused on the CALLY index to elucidate its clinical value. RESULTS: Receiver operating characteristic analysis showed that the area under the curve for the CALLY index was the highest among the four biomarkers. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in the low and the high CALLY groups were statistically significant. Multivariate analysis identified the CALLY index as an independent factor for OS and CSS but not NLR or PLR. The mGPS was an independent factor for OS but not for CSS in multivariate analysis. Regarding complications, only the CALLY index was an independent predictor of major complications (≧ Clavien-Dindo grade 3) in multivariate analysis but not others. CONCLUSIONS: The CALLY index may have a clinical value in predicting OS, CSS, and major complications in GC patients undergoing gastrectomy.

The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. RESULTS: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. CONCLUSION: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.

[A Case of Robot Assisted Low Anterior Resection for a Patient with Persistent Descending Mesocolon].

Persistent descending mesocolon(PDM)is caused by absence of fusion of the descending colon to the retroperitoneum. A 67-year-old man with bloody stools was diagnosed with rectal cancer on colonoscopy. A computed tomography showed a medial displacement of his descending colon. The preoperative clinical diagnosis was rectal cancer with PDM, and robot assisted low anterior resection was performed. We found that the left-sided colon was shifted to the midline and adhered the cecum and the mesentery of small intestine. Robot assisted surgery enables surgery with the precise adhesiotomy in a stable field. PDM is a relatively rare anatomic abnormality. Character of PDM is adhesion between the left-sided colon and other organs and radially branch from the inferior mesenteric artery. It is important to understand the anatomical characteristics of PDM and to improve on existing surgical procedures to ensure safe robot assisted surgery these patients.

[A Case of Double Colorectal Cancer Diagnosed by Preoperative CT Colonography].

A 66‒year‒old man was admitted to our hospital because of anemia and a positive fecal occult blood test in the medical examination. Colonoscopy revealed a type 2 advanced sigmoid colon cancer with circular stenosis. Computed tomography (CT)colonography was performed to examine the oral colon. The apple core signs were found both in the sigmoid and transverse colon. We diagnosed a double colon cancer and performed a laparoscopic left hemicolectomy and sigmoidectomy. The tumor was histopathologically diagnosed as a multiple cancer including a transverse and a sigmoid colon cancer. Although evaluations of the intestine for colon cancer with stenosis are performed by enema examination or endoscopic examination after colon stent placement, both examinations are invasive. CT colonography is considered to be a minimally invasive and an effective preoperative examination for colorectal cancer with stenosis.

[A Case of Advanced Gastric Cancer-Recurrence of Skin Metastasis Nine Years after Surgery and Rectal Stenosis Due to Peritoneal Dissemination Ten Years Later].

A 70-year-old man previously underwent laparoscopic total gastrectomy for gastric cancer in 2010 and pathological diagnoses were pT4a, pN3, M0, pStage ⅢC. The postoperative adjuvant chemotherapy was interrupted due to nausea, but the patient had no apparent recurrence within 5 years after gastrectomy. In 2019, a swelling appeared from the left inguinal region to the scrotum, and MRI scan showed subcutaneous edematous changes in the same region. Biopsy showed adenocarcinoma and we diagnosed a recurrence of gastric cancer with skin metastasis. In November 2020, the patient complained of defecation disorder, and CT scan showed a circumferential wall thickening with contrast effect in the rectum. Although colonoscopy revealed rectal stenosis, biopsy specimen showed no malignant findings. We suspected rectal stenosis due to peritoneal dissemination of gastric cancer and performed a colostomy. Intraoperative findings showed that the rectal wall was remarkably thickened with serosal erythema. Adenocarcinoma cells were found from the cytology of ascites. The patient was treated with nab-paclitaxel plus ramucirumab, then treated with nivolumab after failure of first-line therapy.

[Short- and Long-Term Surgical Outcomes for Patients with Colorectal Cancer Aged 80 Years or Older].

This study aimed to assess short-term and long-term outcomes and to identify the factors that affect outcomes for patients with colorectal cancer aged 80 years or older. Two hundred patients with colorectal cancer who were underwent resection of the primary tumor between January 2013 and December 2018 were enrolled. Short-term outcomes of elderly patients with poor PS and of those who take antithrombotic agents and of those who were underwent open surgery were poor. Long-term outcomes of elderly patients with high GNRI and of those who were underwent D3 lymph nodes dissection were better. Laparoscopic surgery with D3 lymph nodes dissection for elderly patients who were more than 80 years old should be useful to improve short- and long-term outcomes. GNRI might be a prognostic predictive factor for patients with colorectal cancer aged 80 years or older.

[Prognostic Analysis of Colorectal Cancer Patients by the Controlling Nutritional Status(CONUT)Score].

We examined the controlling nutritional status(CONUT)score and the long-term prognosis of colorectal cancer surgery cases. We retrospectively examined the prognosis of colorectal cancer patients who underwent surgery between January 2013 and December 2015. We targeted 449 patients who were able to calculate the CONUT score. A total of 266 patients (59.2%)had normal nutritional status(1 or less)and 183 patients(40.8%)had mildly poor or worse nutritional status (2 or more). The CONUT score was calculated through preoperative blood tests. The relationship between the CONUT score and overall survival was examined in the low and high groups. Overall survival was significantly shorter in the high group but relapse-free survival did not differ significantly between the 2 groups. There was no difference in cancer-specific survival between the 2 groups, but the survival time due to death from other diseases was significantly shorter in the high group. The CONUT score obtained from preoperative blood sampling suggested that the overall survival time was short in the malnourished group, and that it could be used as an index of prognosis due to death from other diseases.

[Short-Term Clinical Outcome of Robotic Surgery for Advanced Rectal Cancer after Neoadjuvant Therapy].

We examined 14 cases who underwent robotic rectal resection with neoadjuvant chemotherapy(NAC)or neoadjuvant chemoradiation therapy(NACRT)for local advanced rectal cancer in our hospital from 2018 June to 2020 December. Two patients underwent NACRT, 12 patients underwent NAC. Sex was 10 males and 4 females. The median age was 66. The surgical procedure was ISR 2 cases, LAR 8 cases, APR 4 cases. The median operation time was 397 minutes and the median blood loss was 73 mL. The histological response grade were Grade 3: 1 case, 2: 7 cases, 1b: 3 cases, and 1a: 3 cases. Surgical margin was negative in all cases. Postoperative complications(≥Clavien-Dindo Grade Ⅲ)required reoperation due to intestinal obstruction in 1 case. Urinary dysfunction was nothing in all cases. Although long-term results such as prognosis and function preservation need to be examined, short-term results of robot-assisted rectal resection after NAC or NACRT were generally good.

[Clinical Significance of Preoperative Chemotherapy for Advanced Colorectal Cancer].

We examined 22 cases who underwent preoperative chemotherapy in our hospital from 2013 April to 2018 December. Seven patients were treated as neoadjuvant chemotherapy(NAC). Out of 15 patients with unresectable diseases before chemotherapy, 6 patients were able to R0 resection after chemotherapy(conversion). Although only one patients was underwent RM1 resection, the other patients were underwent RM0 resection. The median overall survival was 42 months in NAC group, 28 months in conversion group, and 17 months in palliative resection group, respectively. Recurrence was observed in 1 patient in NAC group, however, all patients had recurrent disease in conversion group. In this study, although further examination should be done according to the clinical significance of preoperative chemotherapy, preoperative chemotherapy may be carried out without severe adverse event and severe postoperative complication.

[A Case Report with R0 Resection for Locally Advanced Appendiceal Cancer Invading to the Right External Iliac Vessels].

A 46-year-old man presented with right lower quadrant pain. Enhanced CT revealed a 30 mm sized irregular shaped mass originating from the appendix and invading the abdominal wall. We performed the laparoscopic appendectomy. Finally, the pathologic finding revealed a local advanced appendiceal carcinoma. From the intraoperative findings, the residual tumor was existed around the right external iliac vessels and abdominal wall. The patient was treated with chemotherapy for 13 months. Although the residual tumor encased the right external iliac vessels, the abdominal wall, and psoas major muscle, there were no signs of distant metastasis. We performed ileocecal resection with D3 lymph node dissection. The right external iliac vessels, abdominal wall, and psoas major muscle were resected simultaneously, and reconstructed by femoral- femoral bypass. As a result, R0 resection was achieved pathologically.

Impact of tumor-infiltrating LAMP-3 dendritic cells on the prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells to induce cytotoxic T lymphocytes in the tumor environment. After acquiring antigens, DCs undergo maturation and their expression of MHC and co-stimulation molecules are enhanced, along with lysosome-associated membrane glycoprotein 3 (LAMP-3), which is a specific marker of mature DCs. In general, mature DCs are usually considered to be immunostimulatory in the cancer microenvironment. In addition, it is known that tumor-infiltrating lymphocytes (TILs) are associated with a good prognosis in esophageal squamous cell carcinoma (ESCC). However, few studies have targeted the interaction between DCs and TILs in the local immunity of ESCC. We investigated the localization of mature DCs within ESCC tissue and their relationship to TILs as well as the clinical outcome. METHODS: We evaluated 80 ESCC patients who underwent surgical treatment without preoperative treatment, using immunohistochemistry with LAMP-3 and CD8. RESULTS: The results showed that LAMP-3 DCs were predominantly observed in the peritumoral area. Intratumoral CD8 T cells were found to be associated with a favorable prognosis, and the number of infiltrating LAMP-3 DCs was correlated with the number of intratumoral CD8 T cells. CONCLUSION: At the local tumor site, mature LAMP-3 DCs might be associated with increasing tumor infiltrating CD8 T cells.

Neutrophils in primary gastric tumors are correlated with neutrophil infiltration in tumor-draining lymph nodes and the systemic inflammatory response.

BACKGROUND: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15+neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer. RESULTS: Immunohistochemical staining showed that the median number of CD15+TANs was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs, respectively. Patients were divided into high and low infiltration groups based on the median number. A high number of infiltrating CD15+TANs in the primary tumors and in the TDLNs were associated with depth of invasion and lymph node metastasis. Kaplan-Meier analysis revealed that a poor overall survival was associated with high numbers of CD15+TANs, and the multivariate analyses revealed that a high number of CD15+TANs in the TDLNs was an independent prognostic factor. The numbers of CD15+TANs in the primary tumors and TDLNs showed weak positive correlation. The number of CD15+TANs in the primary tumors was positively correlated with the preoperative NLR, (P = 0.001, R = 0.327) and immunohistochemical staining revealed that C-X-C motif chemokine receptor 2 (CXCR2) +neutrophils might be the origin of the CD15+TANs. Flow cytometry analysis indicated that infiltrating neutrophils increased in the tumor and TDLN compared to non-cancerous tissue. Neutrophils treated with cancer supernatant upregulated TWIST and IL-6 genes in vitro. CONCLUSION: Our findings suggested that local infiltration of CD15+TANs may be correlated with inflammation in TDLNs and systemic response to cause metastasis in gastric carcinoma.

[Significance of Immune-Cell Infiltration in Gastric].

There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL). On the other hand, it has been proved that CD8+ T cells react in an antigen-specific manner even in advanced gastric cancer, suggesting the possibility that memory T cells, NK cells andNKT cells in gastric cancer tissues correlate with goodprognosis. Recently, it has been reportedthat the presence of follicular lymphoidstructure calledtertiary lymphoidstructure(TLS)in gastric cancer tissue is associatedwith favorable prognosis. Although immune responses are suppressedin gastric cancer tissues, the effectiveness of an immune checkpoint inhibitor(anti-PD-1 antibody)has been provedin 2017. The tumor-infiltrating immune cells is known as a predictive effect biomarker. As cancer genome research progresses, which type of immune response is induced is gradually being elucidated in near future. Thus, assessing the invasive morphology and function of various tumorinfiltrating immune cells is considered to be extremely important in Precision Medicine for gastric cancer.

[A case of advanced gastric cancer responding to S-1/CDDP neoadjuvant chemotherapy, leading to a pathological complete response].

A 66-year-old man with cStage III B (cT4aN2H0P0M0) advanced gastric cancer in the cardia with esophageal invasion was treated with S-1/CDDP as neoadjuvant chemotherapy. After 3 courses of chemotherapy, a significant reduction in tumor burden was observed. Total gastrectomy and splenectomy with lymph node dissection (D2) were performed. Pathological specimens showed no cancer cells in the stomach and lymph nodes, indicating a pathological complete response.

[A case of rectal cancer with brain metastasis successfully treated with combined modality therapy - a case report].

The authors report their experience in a patient with brain metastasis from rectal cancer who has survived without recurrence after multidisciplinary treatment. A 60-year-old man presented to the Department of Neurosurgery with the primary complaint of spasm of the left side of the face. Examination revealed a tumor 2 cm in diameter in the right frontal lobe. The tumor was suspected to be metastatic, and brain metastasis from rectal cancer was diagnosed. The brain tumor was removed by a neurosurgeon, and the patient was transferred to the Department of Surgery. Removal of the primary lesion in the rectum was attempted, but only colostomy could be performed due to extensive anterior invasion. Postoperatively, 5 courses of capecitabine and oxaliplatin (XELOX) + bevacizumab were administered. The rectal tumor shrank in size, while another mass, suspected to be a lung metastasis, remained unchanged. Therefore, a second surgery on the rectum was scheduled, and abdominoperineal resection of the rectum and lateral lymphadenectomy were performed. Postoperatively, 4 courses of XE LOX therapy were administered. The patient is currently alive without recurrence at 1 year after surgery. Treatment (including timing) for brain metastasis from rectal cancer has not been established and prognosis is poor. However, multidisciplinary treatment may provide the possibility of cure.

Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model.

The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents.

Study of Short-Term and Long-Term Outcomes Between Esophagogastrostomy and Double-Tract Reconstruction After Proximal Gastrectomy.

BACKGROUND: As the opportunities for proximal gastrectomy (PG) for early gastric cancer in the upper third stomach have been increasing, the safety and feasibility of PG have been a great concern in recent years. This study aimed to compare the short-term and long-term outcomes between patients who underwent esophagogastrostomy (EG) and those who underwent double-tract reconstruction (DTR) after PG. METHODS: We retrospectively reviewed the medical records of 34 patients who underwent EG and 39 who underwent DTR at our hospital between 2011 and 2022. We compared the procedure data and postoperative complications including anastomotic complications within 1 year after surgery as short-term outcomes and the rates of change in nutritional status, skeletal muscle mass, and 3-year survival as long-term outcomes. RESULTS: Although operation time of the DTR group was significantly longer than that of the EG group, there were no significant differences in postoperative complications between 2 groups. Regarding the endoscopic findings, the incidence of anastomotic stenosis and reflux esophagitis was significantly higher in the EG group than in the DTR group (26.5% vs 0%, p < 0.001; 15.2% vs 0%, p = 0.020). In long-term outcomes, there were no significant differences in body weight, BMI, laboratory data, and skeletal muscle mass index between 2 groups for 3 years. The 3-year overall survival rates of 2 groups were similar. CONCLUSION: DTR after PG could prevent the occurrence of anastomotic complications in comparison to EG. The long-term outcomes were similar between these 2 types of reconstruction.

Effectiveness of Nutritional Guidance Focusing on Leucine Intake During Cardiac Rehabilitation Maintenance.

Objective: Due to the lack of information on the effects of nutritional guidance focused on leucine intake in patients undergoing maintenance cardiac rehabilitation, this study investigated on plasma leucine concentrations, lean body mass, and muscle strength. Methods: Nutritional guidance, focused on leucine (intervention group) or general nutritional guidance (control group), was provided for six months to patients participating in cardiac rehabilitation. Body composition, grip strength, hematological test results, and diet of both groups were compared before and after the intervention. Results: Seven patients in the intervention group (53.2 ±â€…18.2 years) and 7 patients in the control group (58.6 ±â€…15.3 years) were included. Dietary survey results showed that the six-month intervention significantly (p < 0.05) increased protein intake and estimated leucine intake only in the intervention group. There was no significant difference in the rate of change in plasma leucine concentration between the two groups. The rate of change in lean body mass was significantly higher in the intervention group compared to the control group (p = 0.035). The rate of change in plasma leucine concentration and that in lean body mass was positively correlated only in the intervention group (r = 0.777, p = 0.040), and the rate of change in plasma leucine concentration was also positively correlated with the rate of change in grip strength (ρ = 0.857, p = 0.014). Conclusions: In the patients undergoing maintenance cardiac rehabilitation, increased plasma leucine concentration by nutritional guidance focused on leucine increased lean body mass without any increasing the training load.

CDDP-induced desmoplasia-like changes in oral cancer tissues are related to SASP-related factors induced by the senescence of cancer cells.

The tumor microenvironment (TME) concept has been proposed and is currently being actively studied. The development of extracellular matrix (ECM) in the TME is known as desmoplasia and is observed in many solid tumors. It has also been strongly associated with poor prognosis and resistance to drug therapy. Recently, cellular senescence has gained attention as an effect of drug therapy on cancer cells. Cellular senescence is a phenomenon wherein proliferating cells become resistant to growth-promoting stimuli, secrete the SASP (senescence-associated phenotypic) factors, and stably arrest the cell cycle. These proteins are rich in pro-inflammatory factors, such as interleukin (IL)-6, IL-8, C-X-C motif chemokine ligand 1, C-C motif chemokine ligand (CCL)2, CCL5, and matrix metalloproteinase 3. This study aimed to investigate the desmoplasia-like changes in the TME before and after cancer drug therapy in oral squamous cell carcinomas, evaluate the effect of anticancer drugs on the TME, and the potential involvement of cancer cell senescence. Using a syngeneic oral cancer transplant mouse model, we confirmed that cis-diamminedichloroplatinum (II) (CDDP) administration caused desmoplasia-like changes in cancer tissues. Furthermore, CDDP treatment-induced senescence in tumor-bearing mouse tumor tissues and cultured cancer cells. These results suggest CDDP administration-induced desmoplasia-like structural changes in the TME are related to cellular senescence. Our findings suggest that the administration of anticancer drugs alters the TME of oral cancer cells. Additionally, oral cancer cells undergo senescence, which may influence the TME through the production of SASP factors.

How do we prevent severe intra-abdominal infectious complications following minimally invasive gastrectomy for cancer? The usefulness of a novel marker using computed tomography images (minimum umbilicus-vertebra diameter) and robotic surgery.

Background: Intra-abdominal infectious complications (IAICs) following minimally invasive gastrectomy (MIG) for cancer sometimes worsen short- and long-term outcomes. In this study, we focused on the minimum umbilicus-vertebra diameter (MUVD) in preoperative computed tomography (CT) images and robotic surgery to prevent severe IAIC occurrence. Patients and Methods: A total of 400 patients with gastric cancer who underwent 204 laparoscopic gastrectomy (LG) and 196 robotic gastrectomy (RG) procedures were enrolled in this study. We retrospectively investigated the significance of the MUVD and robotic surgery for preventing severe IAICs following MIG using multivariate and propensity score matching analysis. Results: The MUVD cutoff value was 84 mm by receiver operating characteristic (ROC) curve using severe IAICs as the end point. The MUVD and visceral fat area (VFA) had significantly higher area under the curve (AUC) than BMI (MUVD vs. BMI, p = 0.032; VFA vs. BMI, p < 0.01). In the multivariate analysis, high MUVD (HR, 9.46; p = 0.026) and laparoscopic surgery (HR, 3.35; p = 0.042) were independent risk factors for severe IAIC occurrence. In the propensity matching analysis between robotic and laparoscopic surgery in the high MUVD group, the RG group tended to have a lower severe IAIC rate than the LG group (0% vs. 9.8%, p = 0.056). Conclusion: The MUVD was a novel and easy-measuring predictor of severe IAICs following MIG. Robotic surgery should be considered first in patients with gastric cancer having an MUVD value of 84 mm or higher from the perspective of severe IAIC occurrence.